In our currently funded project (R01 AG033906), we propose to: 1) characterize ethnic differences in experimental pain sensitivity, endogenous pain inhibition, clinical pain and pain-related disability among older African Americans and non-Hispanic whites with knee osteoarthritis (OA);2) to determine ethnic group differences in biological, psychological, and sociocultural factors and their contribution to pain sensitivity, pain inhibition, and clinical pain and disability among older African Americans and non-Hispanic whites with knee OA;and 3) to determine whether the combination of laboratory measures of pain sensitivity and pain inhibition along with biological, psychological and sociocultural factors mediate ethnic group differences in clinical pain and pain-related disability among older African Americans and non-Hispanic whites with knee OA. In this competitive revision application, which is responsive to NIH notice NOT-OD-09-058, Recovery Act Funds for Competitive Revision Applications, we propose an important expansion of the scope of the original project. Specifically, the currently funded project involves only the recruitment of African American and non-Hispanic white patients with knee osteoarthritis (OA), and the revision proposes to recruit a cohort of older African American and non-Hispanic white control subjects without knee OA. This will allow us to accelerate the tempo of the science by accomplishing two novel and important scientific aims: 1) characterizing ethnic differences in pain sensitivity and endogenous pain inhibition previously observed in healthy young adults in an older control population of African Americans and non-Hispanic whites;and 2) demonstrating in a large multi-ethnic sample that patients with knee OA exhibit significantly greater laboratory pain sensitivity and reduced endogenous pain inhibitory function compared to age and sex matched controls without knee OA. During the previous funding cycle, we produced substantial evidence documenting differences in experimental pain sensitivity and endogenous pain modulation among healthy young African Americans, Hispanic Americans, and non-Hispanic whites. Relative to non-Hispanic whites, both minority groups evinced significantly greater sensitivity to suprathreshold heat, cold, and ischemic stimuli. Moreover, compared to non-Hispanic whites, African Americans showed reduced diffuse noxious inhibitory controls (DNIC), suggesting diminished pain inhibitory capacity. However, these data were collected in young adults, and it is important to demonstrate that similar ethnic group differences in pain sensitivity and pain inhibition are present in older African Americans and non-Hispanic whites. Moreover, no investigator to date has determined in a multi-ethnic cohort whether knee OA patients exhibit generalized hyperalgeisa and impaired pain inhibitory capacity. Support for our hypotheses will provide novel information regarding ethnic differences in pain sensitivity and pain inhibition and will provide the first evidence of alterations in endogenous pain modulation among older African Americans and non-Hispanic whites with knee OA. PUBLIC HEALTH RELEVANCE: Ethnic differences in clinical pain and pain-related disability have been well documented, and ethnic differences in experimental pain sensitivity have been reported among healthy young adults. The goal of this competitive revision is to determine whether ethnic differences in laboratory measures of pain sensitivity and pain inhibition are present among pain-free older African Americans and non-Hispanic whites. In addition, we intend to demonstrate for the first time in a large multi-ethnic sample, that patients with knee OA exhibit significantly greater laboratory pain sensitivity and reduced endogenous pain inhibitory function compared to age and sex matched controls without knee OA.